Hewitt R, Cordaro JA, Gugino LJ, Maliszewski M, Colomaio R, O'Donnell A, Shelton M, Bartos L, Morse GD; International Conference on AIDS.

Int Conf AIDS. 1992 Jul 19-24; 8: 90 (abstract no. PuB 7246).

Center for Clinical Pharmacy Research, State University of New York, Buffalo.

OBJECTIVE: To examine zidovudine (ZDV) pharmacokinetics in HIV-infected women with CD4+ cell counts greater than 200/mm3. METHODS: ZDV pharmacokinetics were studied in 5 stable (mean CD4+ count 608 +/- 426/mm3), asymptomatic HIV-positive women (mean age 25.4 +/- 3.3 yrs) at the onset of their menstrual cycle who were receiving chronic ZDV therapy (300-500 mg/day). Pharmacokinetic parameters were determined in a fasted state after a single 100mg oral dose. Blood samples were collected over an 8 hour period and plasma was analyzed by radioimmunoassay for ZDV and ZDV-glucuronide (GZDV). RESULTS: The mean ZDV concentration prior to the 100 mg dose was 16.2 +/- 14.9 ng/ml (last prior dose taken greater than or equal to 8 h before study). The mean peak ZDV plasma concentration was 519 +/- 166 ng/ml, declining to 39 +/- 9 ng/ml at 4 hours. The mean ZDV area under the concentration versus time curve (AUC) was 1051 +/- 274 ng.h/ml. The mean oral clearance (Cloral = Dose/AUC) was 27.2 +/- 7.0 ml/min/kg. ZDV declined in a biexponential fashion, with a prolonged elimination phase detected from 4 to 8 hours (mean t1/2 = 8.4 +/- 8.3 h). The mean peak GZDV plasma concentration was 2454 +/- 480 ng/ml declining to 131 +/- 57 ng/ml at 4 hours. The mean GZDV AUC was +/- 4222 +/- 961 ng.h/ml and the mean peak GZDV to ZDV ratio was 5.0 +/- 0.9 with a mean 4 hour value of 4.0 +/- 0.6. CONCLUSION: These data indicate that ZDV plasma concentrations are detectable 8 hours after a 100 mg oral dose, and that a prolonged elimination phase is present after 4 hours. The Cloral was not significantly different from male patients but displayed considerable interpatient variability. Further studies evaluating ZDV disposition during the follicular and luteal phase of the menstrual cycle are ongoing.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• CD4 Lymphocyte Count
• Female
• HIV
• HIV Infections
• HIV Seropositivity
• Humans
• Luteal Phase
• Male
• Menstrual Cycle
• Single Person
• Zidovudine
• pharmacokinetics

Other ID:

• 92404535

UI: 102202249

From Meeting Abstracts